BETHESDA, Md--The FDA's Oncologic Drugs Advisory Committee (ODAC)
has unanimously recommended approval of SmithKline Beecham's Hycamtin
(topotecan HCl) for the treatment of patients with metastatic
ovarian cancer after failure of initial or subsequent chemotherapy.
Hycamtin is the first topoisomerase I inhibitor to be recommended
for approval in the United States. This new class of drugs kills
cancer cells by inhibiting the enzyme toposiomerase I, which is
essential in the replication of DNA.
At the ODAC hearing, Colin Broom, MD, of SmithKline Beecham, said
that ovarian cancer is diagnosed in an estimated 26,700 women
each year in the United States, and about 14,800 US women die
annually from the disease. About 30% to 50% of women treated for
ovarian cancer will relapse, with the recurring cancer often resistant
to the original chemotherapy. Second-line drugs are then needed
to treat the recurrence.
Dr. Eric Rowinsky, of Johns Hopkins Oncology Center, described
three phase I trials examining safety and pharmacology. He said
that the major toxicity of Hycamtin is hematological, particularly
neutropenia. He noted that, based on these studies, a phase II
dose was recommended and consistently used in all the trials.
Maurie Markman, MD, of the Cleveland Clinic Cancer Center, speaking
in support of the new drug application (NDA), summarized the results
of the phase I trial (039), an open, randomized, multicenter study
that compared Hycamtin with Taxol (paclitaxel) in 226 women with
recurrent ovarian cancer after first-line platinum therapy.
Patients were randomized to either a 30-minute IV infusion of
Hycamtin, 1.5 mg/m²/day for 5 days, or to a 3-hour infusion
of paclitaxel, 175 mg/m², every 21 days.
The objective response rate (complete response plus partial response)
was 20.5% for Hycamtin vs 13.2% for paclitaxel, with a median
duration of response of 32.1 weeks for Hycamtin vs 19.7 weeks
for paclitaxel. The median time to progression was 23.1 weeks
for Hycamtin vs 14 weeks for paclitaxel (P = .0021). Median survival
was 61.3 weeks for Hycamtin vs 42.6 weeks for paclitaxel (P =